Macaques immunized with uninfected human cells have been shown to be protected from challenge with SIV propagated in human cells. To identify the potential antigens involved in this protection, macaques were immunized with uninfected human cells (HuT 78/H9), beta-2 microglobulin, and HLA class I and class II proteins purified from these human cells. Although all macaques developed high antibody titers to the proteins with which they were immunized, only macaques immunized with class II protein (HLA-DR) developed antibodies to class II and were protected from an intravenous virus challenge. These results were the first demonstration that immunization with a purified cellular protein can protect from virus infection (Arthur et al., J. Virol. 69 3117-3124, 1995). We would like to extend these xenoimmunization studies to study the role of macaque class II antigens in protecting from AIDS virus infection. We intend to identify class II alleles in the pigtailed macaque colony at the WaRPRC and to purify class II DR using the same techniques that led to the purification of HLA DR. Macaques that share similar and distinct class II alleles will be immunized with this purified DR and then challenged with SIVmne grown in lymphocytes from the animal from which the class II antigen was purified. These studies will further address whether antibodies to class II correlate with protection from infection in an alloimmunization regimen, and may help explain why some individuals in some cohorts (e.g., prostitutes in Gambia) are resistant to infection. The results of this study may also be applicable to the design of an AIDS vaccine. To date 10 macaques have been identified for use on this project.